Overall rationale: There is strong evidence in the literature that cellular responses a critical time window over a few day after bone marrow damage from radiation or other genotoxic stress can determine delayed onset disease including bone marrow failure and cancers. We propose that key process may be the formation and persistence of senescent cells, leading to a chronic inflammatory response that drives long-term bone marrow damage, genomic instability and malignance. By acting early to promote DNA repair and suppress onset of senescence, it may be possible for the bone marrow to fully recover before the destructive process can get underway.

Search Data using

Maxquant at 1FDR (Against Mus Fasta, with Secreted against (Mus, Bovine, Feline Fastas).

NR/Ctrl for (IR, NIR, IR_Sec, NIR_Sec)

Median Normalize Data sets

Search Upregulated proteins above Log2 >= 0.26

1. Reactome for Super Pathway enrichment (Plot– log10FDR, #Hits (Proteins)) https://reactome.org/

2. gProfiler for (GOBP, GOMF, GOCC, and KEGG) https://biit.cs.ut.ee/gprofiler/gost

Plot –log10(Adj P-value or FDR)

For Bone Marrow IR Pathway, pull out pathway hits and plot XY (IRNR/IR x-axis, NIRNR/NIR y-axis)

1. Immune Response

2. Redox or Oxidative Stress

3. Stress Response (“Stress”)

4. Apoptotic Cell Death

5. DNA Damage

6. DNA Repair

7. Chromatin Organization

For interesting hits pull out pathway genes and use String-db to obtain network